The authors would like to acknowledge the excellent assistance of Christy Bennet and Ned Realiza. This study was supported by a grant from Nutritional Therapeutics, Inc. Dr. Berns was previously a consultant for Nutritional Therapeutics, Inc.

ABSTRACT. Decreased mitochondrial function is a characteristic of aging and fatigue. Here we determined if mild to moderately severe fatigue in a group of aged subjects (mean age> 60 years), as defined by the validated Piper Fatigue Scale (PFS), can be significantly improved by use of a glycophospholipid dietary supplement, NT Factor™ (NTF). In addition, we determined if mitochondrial function, as defined by transport of the redox dye Rhodamine-123, is reduced in aging subjects with mild to moderately severe fatigue, and if this can be reversed with NTF supplementation in concert with improvement in fatigue scores. Participants with mild to moderately severe fatigue, who fulfilled the entry requirements were admitted to the study when their fatigue could not be explained by an obvious clinical condition.

Twenty of the respondents (mean age = 68.9 +/-
4.18) completed the first part of the study on NTF for 12 weeks, and 16 of these subjects who agreed to discontinue the product also completed a wash-out period for an additional 12 weeks. Fatigue and mitochondrial function were determined every four weeks during the study. There was a time-dependent reduction in overall fatigue in moderately fatigued subjects (P < .001) but not in mildly fatigued subjects. Mitochondrial function at four and eight weeks of NTF use in moderately fatigued subjects increased by 15% and 26.8%, respectively, and restored mitochondrial function to levels similar to those found in young adults. No further increase was noted between 8 and 12 weeks. Post-NTF there was a slow redevelopment of fatigue and a fall in mitochondrial function in moderately fatigued subjects, indicating that continued use of NTF may be necessary to maintain lower fatigue scores and maintain mitochondrial function.

The dietary supplement with NTF reduced moderate fatigue and increased mitochondrial function in aged subjects but had no effect upon mild fatigue expression.

KEYWORDS. Mitochondrial metabolism, NT Factor, Fatigue, Aging

INTRODUCTION

The most common complaint of patients in general medical practice is fatigue (1), and in fact, chronic fatigue is reported by 20% of all patients seeking medical care (1,2). Many well-known medical conditions are associated with chronic fatigue (3), and it is often an important secondary condition in many clinical diagnoses. Loss of energy and the symptom of fatigue often precede a clinical diagnosis, and this may be one reason that it is so commonly reported by patients seeking medical care.

Fatigue is thought to be a multidimensional sensation with many possible causes and no universally accepted definition. Piper et al. (4) described fatigue as a multi-component sensation with behavioral, affective, sensory and cognitive components. They also designed a simple measurement model that combined multiple fatigue-associated elements into an overall fatigue score (4).

At the cellular level, fatigue is involved with cellular energy systems that for the most part are found in the mitochondria. Damage to cellular mitochondria can impair the abilities of cells to produce ATP and reduced NAD, and this occurs naturally with aging. Major targets of mitochondrial damage are phospholipid/protein membranes and mitochondrial DNA (5-7). For example, damage of phospholipids in mitochondrial membranes by free radicals can affect membrane integrity, fluidity and transmembrane potentials, resulting in loss of energy production by the electron transport chain and its associated components. During the aging process mitochondria suffer damage to their membranes and DNA, and this is thought to contribute to or even be a cause of the aging process (8,9).

Preventing cell membrane damage and loss of membrane integrity are important in prevention of loss of cellular energy. One method that has been used to replace damaged mitochondrial membrane phospholipids is replacement therapy, and this has been accomplished, in part, by replacement of damaged lipids using a dietary supplement containing polyunsaturated phosphatidylcholines and other phospholipids and fatty acids that are essential structural and functional components of all biological membranes (10-12).

In previous studies, a dietary supplement, NT Factor™ (NTF) in a vitamin and mineral mixture (Propax™), was used to reduce chemotherapy-induced fatigue, nausea, vomiting and other side effects associated with chemotherapy (10). NTF was also used to protect from hearing loss associated with aging and prevent mitochondrial membrane potential changes and mitochondrial DNA deletions that occur with aging (11). We used Propax plus NTF in a pilot study with severely fatigued, aged subjects to reduce fatigue, as measured by the Piper Fatigue Scale (PFS). We found that fatigue was reduced 33%, from severe to moderate fatigue, after eight weeks of using Propax™ containing NTF (12).

The present study was initiated to examine the effects of NTF on fatigue in moderately and mildly fatigued subjects and to determine if their mitochondrial function, as measured by the transport and reduction of Rhodamine-123 (13), improved with administration of NTF in concert with improvements in fatigue scores.